Cryogenic storage device comprising a transponder

ABSTRACT

A method for operating a cryostorage device ( 100 ), especially for biological samples, is described which comprises a sample carrier ( 10 ) to receive at least one sample ( 11 ) and a data storage ( 20 ), wherein data are inductively transmitted from the data storage device ( 20 ) into a wireless transmission channel ( 40 ) and/or conversely using a resonant circuit ( 30 ) connected to the data storage device ( 20 ).

BACKGROUND OF THE INVENTION

The invention relates to methods for operating a cryostorage devicewhich is arranged for storage and/or preservation of especiallybiological samples, and especially methods for data transmission duringcryostorage as well as cryostorage devices for implementing suchmethods.

Cryostorage is a generally known technique for the storage and/orpreservation of samples having a temperature-sensitive lifetime orstability, such as biological samples for example. Depending on thespecific task, animal or vegetable products, organs of living beings orparts of biological systems, such as cells, cell constituents,macromolecules, micro-organisms, viruses or the like are transferred toa reduced-temperature state and stored. For preservation over longperiods of time storage preferably takes place at liquid-nitrogentemperature or in a nitrogen-vapour atmosphere.

Patent applications DE 100 60 889 and DE 101 44 925 unpublished at thepriority date of the present patent application, describe devices forthe cryostorage of microscopically small biological samples. In these itis especially provided to deposit the samples in a cryostorage deviceeach together with sample data which are characteristic to the relevantsamples. There is a need to read or supplement the sample data in thedata storages whilst the sample is in the cryopreserved state. Dependingon the storage principle of the sample data, data-bus-bound or opticalaccess to the data storage device has conventionally been realised. Thismay have the disadvantage that the handling capability of thecryostorage can be limited.

In data transmission technology transponder systems are increasinglyreplacing the conventional identification of objects using bar codes.Applications for example are known in automated production (automobileindustry), monitoring technology (access control), in living animalidentification or route tracking (e.g. courier services). Transpondershaving a wide range of designs matched to the particular application areknown (for a review see K. Finkenzeller “RFID Handbook”, Hanser-Verlag,Munich, 2000).

The term transponder as an abbreviation of “transmitter” and “responder”designates a transmitting and receiving device which shows a reaction,e.g., gives an answer to a received and evaluated enquiry. In general, atransponder comprises a resonant circuit and an integrated circuit witha data storage device (e.g. EEPROM). Data transmission from the datastorage (transponder storage) via a wireless transmission channel e.g.to a central control system takes place by using the resonant circuit asa transmitting or receiving antenna. The resonant circuit is tuned to acertain transmitting or receiving frequency (e.g. 62 kHz). For powersupply especially during the write/read process the transponder isexposed to an electromagnetic alternating field at a differentfrequency, e.g., twice the frequency (e.g. 124 kHz) with which a currentis induced in the resonant circuit. Transponders typically have a rangeof around 80 cm. The circuit typically contains a voltage regulator, afrequency divider and an encoder.

Advantages of transponders consist in their miniaturisability and accesssecurity. For example, space-saving transponders in foil form (so-calledsmart labels such as the “Tag-it” transponders from Texas Instruments)are known. Authentification and encryption methods are known forimplementing access security. One problem with transponder systemshowever is that their transmission function is sensitively dependent onthe ambient conditions. For example, metallic materials and strongelectromagnetic foreign fields in the vicinity can limit the range oftransponders to around 20 cm. For this reason, the use of transpondersystems has so far been limited to the afore-mentioned tasks withsufficiently well controllable ambient conditions.

The object of the invention is to provide an improved method with whichthe above disadvantages of conventional cryostorage methods are overcomeand which have a simplified handling capability and an extended range ofapplication. Methods according to the invention should especially makeit possible to achieve fast and secure access to sample data regardlessof the operating state of a cryostorage device. The object of theinvention is also to provide apparatus for implementing the method.

These objects are solved by methods and apparatus of the invention.

SUMMARY OF THE INVENTION

The basic idea of the invention is, in a method for cryostorageespecially of biological samples, to transmit data using at least oneresonant circuit inductively between at least one data storage which isprovided on a sample carrier for receiving at least one sample, and awireless transmission channel. The combination according to theinvention of a data storage for the cryostorage with a resonant circuitadvantageously solves the above object by the fact that a plurality ofcryostorage devices can be operated simultaneously under cryogenicconditions and the relevant data can be written and/or read withoutthere being a need to provide a special connection of the cryostoragedevices to an optical transmission section or bus connection. Data canbe transmitted in the cooled state of the sample under conditionsidentical to the specific storage conditions. Advantageously, the datatransmission can take place at temperatures below −40° C. In general,the resonant circuit is formed by an induction element via which thedata storage can interact with the electromagnetic transmission channel.

According to a preferred embodiment of the invention the data aretransmitted using a transponder which contains the data storage as atransponder storage and the resonant circuit. The inventor hasestablished for the first time that inherently known transponders cansurprisingly be used under extreme operating conditions such as duringcryopreservation. This particularly applies to operation at atemperature below −60° C. or lower and in cooling containers for holdingcooling media. Cooling containers are frequently multi-wall vesselshaving a complex structure in whose interior at least one transpondersystem is operated according to the invention. The transponder storagecan advantageously take on the function of the data storage for sampledata so that the structure of the cryostorage device is simplified.

Particular advantages with regard to a simplified structure are obtainedif the data storage, an additional data processing unit and/or anotherfunctional element of the cryostorage system can be supplied with energyvia the transponder. The functional element can for example be ameasuring element or an actuating element for manipulation (processingor treatment) of a cryosample.

According to an advantageous embodiment of the method according to theinvention, the resonant circuit is connected via the electromagnetictransmission channel to a transmission antenna from which the data aretransmitted to a control and evaluation device. Preferably onetransmission antenna is jointly used by a plurality of cryostoragedevices according to the invention, whose resonant circuits are tuned tothe transmission antenna. In this case, the transmission antenna isadvantageously permanently or temporarily arranged in or on an edge of acooling container to receive a plurality of cryostorage devices.

The data transmitted according to the invention preferably comprisesample data with which the sample is identified and characterised,process data characteristic of the storage conditions of the sample sofar, control data with which predetermined operating states of thecryostorage device are adjusted or triggered, and/or additional datasuch as e.g. personal data and diagnostic results.

The applicability of the invention goes far beyond the conventionalidentification function of transponders and represents a substantialadvantage compared with conventional transponder applications. Accordingto particular embodiments according to the invention, it is evenpossible to implement control circuits in which the sample data containmeasured values which have been obtained on the samples in thecryostorage device and the control data are adjusted using the controland evaluation device depending on the measured values.

A subject of the invention is also a cryostorage device, especially forthe storage of biological samples in the frozen state which comprises atleast one sample carrier to receive at least one sample and at least onedata storage wherein at least one resonant circuit which is providedwhich is connected to the data storage and is set up to transmit datainductively from the data storage device into a wireless transmissionchannel and/or conversely.

According to a preferred embodiment of the cryostorage device accordingto the invention, the resonant circuit is part of a transponder whichcomprises a data storage and the resonant circuit. The data storage isexclusively a transponder storage as is inherently known fromconventional transponders or a data storage which fulfils both functionsof a transponder storage and a sample data storage. The data storage canthus advantageously fulfil a plurality of functions. The structure of acryostorage device is simplified. The data storage can also beintegrated in a data processing unit which is respectively allocated toa sample carrier.

A subject of the invention is also a cryostorage system with a pluralityof cryostorage devices which each have said structure. The cryostoragesystem is furthermore equipped with a transmission antenna which isjointly tuned to all cryostorage devices and a control and evaluationdevice. Data can be transmitted between the control and evaluationdevice and respectively one data storage via the allocated resonantcircuit and the transmission antenna which is connected to the controland evaluation unit in a conducted or wireless fashion. The cryostoragesystem is preferably arranged in a thermally insulated container toreceive a cooling medium, especially liquid nitrogen.

The invention has the following further advantages. The invention ishighly adaptable to the specific formulation of the problem. It ispossible (i) to uniquely identify the samples (identification) and readout the identification information without contact (read transpondersonly), (ii) to store the data directly at or on the sample without therebeing a need for an own conducted power supply at the sample, and (iii)data can be read and written without contact and if necessary undercryogenic conditions (write-read transponder). Furthermore, anon-contact power supply can be provided (passive transponder) for thefirst time for sensors (measuring device) present on the cryostoragedevice.

The data transmission and power supply implemented without contactprovides new advantages which were not present with earlier applicationsof transponders. Thus, access to the cryosample with high-frequencyelectromagnetic fields can be provided through protective packaging(e.g. through foils) and thermal insulation. The non-contact operationprevents any limitation of lifetime by wear, corrosion or contamination.A high failure safety is given so that despite a possibly high number ofwrite and/or read processes on the data storage, longevity of thecryosample in the region of years is guaranteed. Inductive access tosample data is especially possible in the cryopreserved state of thesample.

The non-contact operation also avoids any potential heating effect whichcould occur as a result of the conducted or optical writing in ofinformation in conventional techniques. The stability of the cryosampleis increased.

The invention makes it possible to operate cryostorage systems with alarge number of cryostorage devices. Transponders can be used in massproduction with high economic efficiency. Transponder systems allowhigh-grade parallel operation which is especially advantageous fortracking many samples or search functions.

BRIEF DESCRIPTION OF SEVERAL VIEWS OF THE DRAWINGS

Further advantages and details of the invention can be seen from thedescription of the appended drawings. In the figures:

FIG. 1 is a schematic illustration of an embodiment of a cryostoragedevice according to the invention,

FIG. 2 is another embodiment of a cryostorage device according to theinvention, and

FIG. 3 is a schematic illustration of an embodiment of a cryostoragesystem according to the invention, with a plurality of cryostoragedevices.

DETAILED DESCRIPTION OF PREFERRED EMBODIMENTS

A cryostorage device 100 according to the invention as shownschematically in FIG. 1 comprises a sample carrier 10 to receive atleast one sample 11, a data storage 20 and a resonant circuit 30 whichis connected to the data storage device 20 and the sample carrier 10.The sample carrier 10 is connected to the data storage 20 as isdescribed for example in the afore-mentioned unpublished patentapplications. The samples 11 are preferably formed by biologicalsamples. Preferably provided are miniaturised samples withcharacteristic volumes in the nl to μl range which respectively containa sample suspension and biological material such as e.g. cells, cellconstituents, macromolecules, micro-organisms, viruses or the like.Reference samples of biological or synthetic origin can also be providedon the sample carrier 10.

The data storage 20 also forms a carrier for the resonant circuit 30which in the example shown comprises four induction loops 31 which areset up to transmit and/or receive high-frequency electromagneticoscillations in the kHz range (or higher harmonics thereof). Theinduction loops 31 are connected to the data storage 20 as is inherentlyknown for conventional transponders.

The at least one resonance frequency range of the resonant circuit 30forms a transmission channel 40 for high-frequency electromagneticoscillations for data transmission between the cryostorage device 100and a transmission antenna 50. The transmission antenna 50 is for itspart connected in a conducted or wireless fashion to a control andevaluation device 60 or is integrated therein. The reference number 70indicates a cryocontainer which contains at least one cryostorage device100 and a cooling medium and forms a thermal insulation with respect tothe surroundings. The transmission antenna 50 can also be arranged inthe cryocontainer 70 (see FIG. 3).

The data storage device 20 is for example an EEPROM or a so-called Flashmemory which is set up for permanent data storage and is equipped with amicrocontroller. The data storage 20 can also be combined with a dataprocessing device. Both components can be provided as a commonintegrated circuit which is connected to the sample carrier 10.

The induction loops 31 of the resonant circuit 30 are preferablyintegrated using an inherently known coil-on-chip method as transponderantenna directly on the semiconductor material of the data storage 20 orthe encapsulation of a microchip which contains the data storage 20 andpossibly a data processing unit. An additional insulation layer can beprovided to insulate the resonant circuit 30 with respect to the datastorage 20. According to the invention, the sample carrier 10 can alsobe arranged on an inherently known transponder with the data storage 20(transponder storage) and the resonant circuit 30. Unlike the diagram inFIG. 1, the samples 11 can also be arranged next to the resonant circuit30 or on the opposite side of the data storage 20.

Further details of a cryostorage device according to the invention areillustrated for example in FIG. 2. In this embodiment the sample carrier10 comprises hose-shaped chambers to accommodate samples (see DE 101 44925). The sample chambers are affixed to a frame 12 which is fixed tothe encapsulation of an integrated circuit 21 or worked into theencapsulation. The integrated circuit 21 contains a sample data storage.Affixed to the sample chambers is a transponder 32 with the resonantcircuit and a data storage. In this arrangement there is no connectionbetween the transponder 32 and the sample data storage. The transponder32 is used here exclusively to identify the samples. The power and datasupply to the circuit 21 is accomplished however via separate connectingleads 22 with which the data storage plugs for example in a holder viawhich the connection to the control circuit is made. Alternatively anelectrical connection can also be formed between the transponder 31 andthe circuit 21.

In practical use, the cryostorage devices 100 as shown in FIG. 1 or 2are used according to the following principles. After loading the samplecarrier 10 with biological samples, e.g. cell suspensions, the sampledata storage, which is part of the data storage 20, is written withsample data with which the samples are identified and characterised. Thesample data, for example, comprise measured values which were determinedbeforehand for the biological samples as well as information on theorigin and properties of the samples. The data can be written in beforethe cryopreservation via the resonant circuit 30. Alternatively, thedata transmission only takes place after the cryopreservation.

In general the cryopreservation comprises transferring the cryostoragedevice 100 into a reduced-temperature cooling medium such as liquidnitrogen or its vapour. The cryostorage device can also be at leastpartly in contact with the cooling medium during the sample loading andcan have a suitably reduced temperature.

In the cryopreserved state the cryostorage device 100 is stored in thecooling medium. Storage takes place for example in a cooling container70 (see FIG. 3). During storage further data can be transmitted to thedata storage 20. The data comprise, for example process datacharacteristic of the storage conditions of the sample, furthermeasurement data which were obtained on the donor organism of thepreserved samples and/or control data. The process data comprise forexample temperature characteristics which were recorded usingtemperature sensors in the cryocontainer or the surroundings and arestored without contact in the data storage 20. The control data forexample contain control information with which predetermined measurementor manipulation processes can be triggered on the sample. For example,in order to determine the storage state of a sample the measurement of acharacteristic sample parameter can be carried out externally by meansof a start command. The measurement takes place on the cryopreservedsample in the frozen state or alternatively on a locally thawed partialsample. The respective measured values are stored in the data storage20. In addition to said data transmission to the data storage 20(writing) at the cryostorage device data transmission can also takeplace in the reverse direction to the evaluation and control device 60(read). The data transmission preferably takes place using transmissionprotocols such as are inherently known from telemetric applications oftransponders. Telemetric transponders are based on data transmission inthe form of electrical quantities (e.g. frequency, phase, amplitude)which are in a predetermined relationship with the data to betransmitted.

The write and read processes can advantageously also be integrated in afeedback mechanism. In this mechanism measured values from temperaturesensors are initially stored in the data storage 20. The stored data areread out at certain time intervals and used to regulate an externaltemperature control system. According to the locally prevailing storageconditions the sample is thus actively involved in the cryopreservationprocess, the cooling and/or the thawing. Conversely, locally determinedmeasured values can be used to control local thawing of samples orsample parts according to pre-determined temperature profiles or fortreatment or processing of samples, possibly in the locally thawedstate.

Changes to the sample carrier 10 can also be brought about with thecontrol data. For example, for removal of part samples control data aresent to predetermined cryostorage devices which bring about a mechanicalchange on the sample carrier. The mechanical change can for examplecomprise a thermal separation of part of the sample carrier. Diagnosticprocesses on the cryopreserved or locally thawed samples can also betriggered using the control data.

FIG. 3 shows a cryostorage system 200 according to the invention with aplurality of cryostorage devices 100 which are formed for exampleaccording to the embodiments shown in FIG. 1 or 2. Each cryostoragedevice 100 comprises a sample carrier 10 with a data storage 20 which isconnected to a resonant circuit 30. The cryostorage devices 100 arearranged in the cooling container 70 whose outer wall is only partlyshown for reasons of clarity. The cryostorage devices 100 are forexample usually inserted in a shelving system with compartments. Accessto the cryostorage devices 100 or to samples arranged thereon is made bya lock 71 provided in the container wall. Furthermore, a transmissionantenna 50 and a sensor device 80 are provided in the cryocontainer 70.The transmission antenna 50 is connected in a wireless or conductedfashion to the control and evaluation device 60 which is preferablybuilt into the wall of the cooling container 70. The device 60especially contains a display screen (preferably with a possibility fordata entry, for example, a so-called touchscreen screen) and a signaldevice 62 with which operating states of the cryostorage system 200 canbe signalled acoustically or optically. The device 60 also comprises aninterface 63 via which a further wireless connection or networking witha central control system is formed.

Cryopreservation using a system from FIG. 3 takes place for example inliquid nitrogen vapour. Liquid nitrogen is poured into the coolingcontainer 70 as cooling medium 90. A schematically illustrated fillingdevice 73 is provided for this. A temperature of around −120° C. to−170° C. forms in the container volume above the cooling medium 90.Alternatively all the cryostorage devices 100 can be inserted in thecooling medium 90.

A particular advantage of the invention is that the cooling system 200is an independent unit. The cooling container 70 is inherentlyoperational and movable without permanently attached connecting leads.The cooling container 70 can for example be moved on wheels 72.

The features of the invention disclosed in the preceding description,the drawings and the claims can be important both individually and incombination for the implementation of the invention in its variousembodiments.

1. A method for operating a cryostorage device, which comprises a samplecarrier to receive at least one sample and a data storage, comprisingthe step of: inductively transmitting data from the data storage into awireless transmission channel or from the wireless channel to the datastorage using a resonant circuit connected to the data storage, whereinat least one of the data storage and a data processing unit are suppliedwith energy using the resonant circuit.
 2. The method according to claim1, wherein the data are transmitted using a transponder which comprisesthe data storage and the resonant circuit.
 3. The method according toclaim 1, wherein the resonant circuit is connected via the datatransmission channel to a transmission antenna from which the data aretransmitted to a control and evaluation device.
 4. The method accordingto claim 1, wherein the data transmission takes place whilst the atleast one sample is in a cryopreserved state.
 5. The method according toclaim 1, wherein data are transmitted using the resonant circuit whichcomprise at least one of sample data with which the sample is identifiedand characterised, process data characteristic of sample storageconditions so far and control data with which predetermined operatingstates of the cryostorage device are set or triggered.
 6. The methodaccording to claim 5, wherein the sample data contain measured valueswhich have been obtained for the samples or the cryostorage device, andthe control data are adjusted using the control and evaluation devicedepending on the measured values.
 7. The method according to claim 1,wherein the data transmission takes place at temperatures below −40° C.8. A method according to claim 1, wherein a telemetric transponder isused for data transmission in a cryostorage device for biologicalsamples.
 9. The method according to claim 1, wherein the at least onesample is a biological sample.
 10. A cryostorage device comprising: atleast one sample carrier adapted to receive at least one sample, atleast one data storage, and at least one resonant circuit which isconnected to the data storage and is adapted to transmit datainductively from the data storage into a wireless transmission channelor transmit data inductively from the wireless transmission channel tothe data storage, wherein at least one of the at least one data storageand a data processing unit are supplied with energy using the resonantcircuit.
 11. The cryostorage device according to claim 10, wherein theresonant circuit is part of a transponder which comprises the datastorage and the resonant circuit.
 12. The cryostorage device accordingto claim 10, wherein a separate sample data storage is provided.
 13. Thecryostorage device according to claim 10 which contains a dataprocessing unit in which the data storage is integrated.
 14. Thecryostorage device according to claim 10, wherein a transmission antennaand a control and evaluation device are provided wherein data can betransmitted between the data storage and the control and evaluationdevice via the resonant circuit and the transmission antenna.
 15. Thecryostorage device according to claim 10, wherein the sample carrier,the data storage and the resonant circuit are arranged in a thermallyinsulated container for accommodating a cooling medium.
 16. Thecryostorage device according to claim 15, wherein the thermallyinsulated container is adapted for accommodating liquid nitrogen.
 17. Acryostorage system containing a plurality of cryostorage devicesaccording to claim
 10. 18. The cryostorage system according to claim 17,wherein the cryostorage devices are arranged in a cryocontainer with atransmission antenna and a control and evaluation device.
 19. Thecryostorage system according to claim 17, which is equipped with coolingusing liquid nitrogen or liquid nitrogen vapour.
 20. The cryostoragedevice according to claim 10, wherein the device is adapted to storebiological samples in a frozen state.